The administration of CHC13 to phenobarbital pretreated rats produced a 65 percent decrease in liver glutathione (GSH). In contrast, CHBr3 treatment led to only 14 percent depletion of GSH. CHC13 was activated to phosgene (COC12) by rate liver microsomes, which reacted with glutathione (GSH) to produce predominantly diglutathionyl-dithiocarbonate (GSCOSG). CHBr3, however, was converted by microsomes into carbonyl dibromide (COBr2) which reacted with GSH to produce oxidized glutathione (GSSG) and very little GSCOSG. These results indicate that the hepatotoxic metabolites of CHC13 and CHBr3, namely COC12 and COBr2 respectively, react differently with tissue components and therefore may cause tissue necrosis by different mechanisms. By understanding the basis of these differences, a better fundamental knowledge of the events leading to tissue necrosis should be obtained.